NM_001987.5:c.*2799C>T

Variant names:

• chr12-11893845-C-T
• rs540952285
• NM_001987.5:c.*2799C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001987.5(ETV6):​c.*2799C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0080 (21 hom., cov: 18)
  • Exomes 𝑓: 0.00075 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ETV6 NM_001987.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550

Genes affected

ETV6 (HGNC:3495): (ETS variant transcription factor 6) This gene encodes an ETS family transcription factor. The product of this gene contains two functional domains: a N-terminal pointed (PNT) domain that is involved in protein-protein interactions with itself and other proteins, and a C-terminal DNA-binding domain. Gene knockout studies in mice suggest that it is required for hematopoiesis and maintenance of the developing vascular network. This gene is known to be involved in a large number of chromosomal rearrangements associated with leukemia and congenital fibrosarcoma. [provided by RefSeq, Sep 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.000746 (13/17428) while in subpopulation NFE AF= 0.000869 (9/10356). AF 95% confidence interval is 0.000453. There are 0 homozygotes in gnomad4_exome. There are 7 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAdExome4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ETV6	NM_001987.5	c.*2799C>T		3_prime_UTR_variant	Exon 8 of 8	ENST00000396373.9	NP_001978.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ETV6	ENST00000396373.9	c.*2799C>T		3_prime_UTR_variant	Exon 8 of 8	1	NM_001987.5	ENSP00000379658.3

Frequencies

GnomAD3 genomes AF: 0.00801 AC: 783 AN: 97730 Hom.: 21 Cov.: 18

Gnomad AFR AF: 0.00710

Gnomad AMI AF: 0.0145

Gnomad AMR AF: 0.00588

Gnomad ASJ AF: 0.0119

Gnomad EAS AF: 0.00125

Gnomad SAS AF: 0.0171

Gnomad FIN AF: 0.00134

Gnomad MID AF: 0.00455

Gnomad NFE AF: 0.00909

Gnomad OTH AF: 0.00837

GnomAD4 exome AF: 0.000746 AC: 13 AN: 17428 Hom.: 0 Cov.: 0 AF XY: 0.000857 AC XY: 7 AN XY: 8170

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000936

Gnomad4 EAS exome AF: 0.000554

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000869

Gnomad4 OTH exome AF: 0.000765

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00798 AC: 780 AN: 97736 Hom.: 21 Cov.: 18 AF XY: 0.00772 AC XY: 361 AN XY: 46732

Gnomad4 AFR AF: 0.00709

Gnomad4 AMR AF: 0.00578

Gnomad4 ASJ AF: 0.0119

Gnomad4 EAS AF: 0.00125

Gnomad4 SAS AF: 0.0166

Gnomad4 FIN AF: 0.00134

Gnomad4 NFE AF: 0.00909

Gnomad4 OTH AF: 0.00832

Alfa AF: 0.00792 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.5
DANN	Benign	0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs540952285; hg19: chr12-12046779;